FCF Funded Projects

Disruption of PKA RIα phase separation by the oncogenic fusion protein in FLC

Status: Active

Timeframe: 2021 – 2022

Goal: Elucidate the molecular mechanisms of FLC and identify new pharmacological agents that could lead to new, effective therapeutics

Principal Investigator: Jin Zhang, PhD, Vice Chair and Professor of Pharmacology, Department of Pharmacology

In recent studies, the investigation team discovered that the presence of the FLC oncogenic fusion protein disrupts a membraneless organelle. They showed that loss of this membraneless organelle in normal cells results in aberrant signaling as well as increased cell proliferation and transformation. Based on these data, they hypothesize that loss of this membraneless organelle induced by the oncogenic fusion leads to defects in cellular functions and drives tumor formation. The identification of pharmacological agents that recover this membraneless organelle in the presence of the oncogenic fusion protein, could provide useful leads for developing new therapeutics. In this proposed research, the team will test these hypotheses by combining a variety of novel approaches, including live-cell biochemistry. They will undertake mechanistic studies in the established model systems and perform drug screens, in conjunction with additional collaborators with complementary expertise. The study should provide new insights into the cause of FLC and enable new therapeutic strategies to tackle this lethal cancer.